The proline-rich sequence of CD3ε controls T cell antigen receptor expression on and signaling potency in preselection CD4+ CD8+ thymocytes

被引：87

作者：

Mingueneau, Michaeel ^{[1
]}

Sansoni, Amandine ^{[1
]}

Gregoire, Claude ^{[1
]}

Roncagalli, Romain ^{[1
]}

Aguado, Enrique ^{[1
]}

Weiss, Arthur ^{[2
]}

Malissen, Marie ^{[1
]}

Malissen, Bernard ^{[1
]}

机构：

[1] Univ Aix Marseille 2, CNRS UMR 6102, INSERM U631, Ctr Immunol Marseille Luminy, F-13288 Marseille, France

[2] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 05期

关键词：

D O I：

10.1038/ni.1608

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Antigen recognition by T cell antigen receptors (TCRs) is thought to `unmask' a proline-rich sequence (PRS) present in the CD3 epsilon cytosolic segment, which allows it to trigger T cell activation. Using `knock-in' mice with deletion of the PRS, we demonstrate here that elimination of the CD3e PRS had no effect on mature T cell responsiveness. In contrast, in preselection CD4(+)CD8(+) thymocytes, the CD3 epsilon PRS acted together with the adaptor protein SLAP to promote CD3 zeta degradation, thereby contributing to downregulation of TCR expression on the cell surface. In addition, analysis of CD4(+)CD8(+) thymocytes of TCR-transgenic mice showed that the CD3 epsilon PRS enhanced TCR sensitivity to weak ligands. Our results identify previously unknown functions for the evolutionarily conserved CD3 epsilon PRS at the CD4(+)CD8(+) developmental stage and suggest a rather limited function in mature T cells.

引用

页码：522 / 532

页数：11

共 48 条

[1] Initiation of TCR signaling:: regulation within CD3 dimers [J].